Delta opioid delta receptor (DOP) agonists have been proposed as attractive candidates for the novel psychotropic drugs. Therefore, many researchers tried to develop its derivatives. However, these prototype DOP agonists were dropped at the stage of early clinical trials because of undesirable side effects, such as catalepsy and convulsion. We have succeeded in synthesizing a novel selective DOP agonist KNT-127. KNT-127 produced neither undesirable side effects of prototype DOP agonist nor the adverse effects associated with benzodiazepine anxiolytics and SSRI antidepressants. We have demonstrated that KNT-127 has robust anxiolytic-like effect in rodents via inhibition of glutamate signaling in mice prelimbic prefrontal cortex (PFC). We have also demonstrated that KNT-127 exert potent antidepressant-like effects via PI3-mTOR signaling in mice infralimbic PFC. Recent studies indicated that KNT-127 facilitates fear extinction and inhibits reconsolidation of fear memory in mice conditioned fear test. We propose that DOP should be considered as an attractive target for the development of novel psychotropic drugs.